Youth with Attention-Deficit/Hyperactivity Disorder (ADHD) frequently experience academic impairment, including lower grades than their peers and elevated risk for grade retention and school dropout. Medication is the most commonly used treatment for youth with ADHD, and it is therefore essential to understand the extent to which medication use improves long-term academic functioning. This paper reviews the literature on the relation between long-term medication use and the academic outcomes of youth with ADHD. A systematic literature search was conducted to identify pertinent studies published since 2000 that followed youth with ADHD for 3 or more years. Academic outcomes of interest included school grades, achievement test scores, and grade retention. Nine studies were identified reporting on eight distinct longitudinal samples (N across studies = 8,721). These studies demonstrate that long-term medication use is associated with improvements in standardized achievement scores. However, the magnitude of these improvements is small and the clinical or educational significance is questionable. Evidence for long-term improvements in school grades and grade retention is less compelling. This review highlights methodological considerations in providing directions for future research. The importance of using multiple sources to gather information about medication adherence is discussed, including use of methodologies such as electronic monitors, rather than relying solely on parent report or chart review. Future research should also examine a range of medication adherence definitions in order to determine whether age of onset, duration of use, dose, and/or consistency of use moderates the relation between long-term medication use and academic outcomes.